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Stress
The International Journal on the Biology of Stress
Volume 26, 2023 - Issue 1
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Research Article

Examination of the role of adrenergic receptor stimulation in the sensitization of neuroinflammatory-based depressive-like behavior in isolated Guinea pig pups

, , , , , & show all
Article: 2239366 | Received 29 Apr 2023, Accepted 17 Jul 2023, Published online: 06 Aug 2023
 

Abstract

Early-life attachment disruption appears to sensitize neuroinflammatory signaling to increase later vulnerability for stress-related mental disorders, including depression. How stress initiates this process is unknown, but studies with adult rats and mice suggest sympathetic nervous system activation and/or cortisol elevations during the early stress are key. Guinea pig pups isolated from their mothers exhibit an initial active behavioral phase characterized by anxiety-like vocalizing. This is followed by inflammatory-dependent depressive-like behavior and fever that sensitize on repeated isolation. Using strategies that have been successful in adult studies, we assessed whether sympathetic nervous system activity and cortisol contributed to the sensitization process in guinea pig pups. In Experiment 1, the adrenergic agonist ephedrine (3 or 10 mg/kg), either alone or with cortisol (2.5 mg/kg), did not increase depressive-like behavior or fever during initial isolation the following day as might have been expected to if this stimulation was sufficient to account for the sensitization process. In Experiment 2, both depressive-like behavior and fever sensitized with repeated isolation, but beta-adrenergic receptor blockade with propranolol (10 or 20 mg/kg) did not affect either of these responses or their sensitization. The high dose of propranolol did, however, reduce vocalizing. These results suggest sympathetic nervous system activation is neither necessary nor sufficient to induce the presumptive neuroinflammatory signaling underlying sensitization of depressive-like behavioral or febrile responses in developing guinea pigs. Thus, processes mediating sensitization of neuroinflammatory-based depressive-like behavior following early-life attachment disruption in this model appear to differ from those previously found to underlie neuroinflammatory priming in adults.

Disclosure statement

The authors have no conflicts of interest to report.

Data availability statement

The data that support the findings of this study are available from the corresponding author, MBH, upon reasonable request.

Additional information

Funding

This work was supported by Grant HD100825 from the National Institute of Child Health and Human Development.